More than a billion people in 80 mid- and low-income countries of Africa, Asia and the Pacific are at risk for lymphatic filariasis (LF), a mosquito bore parasitic worm Neglected Tropical Disease (NTD) that causes elephantiasis, disfigurement of the male genitalia and painful swelling of the extremities. For the past 10 years there has been intense global effort to eliminate LF due to Wuchereria bancrofti (Wb) with a target date of 2020 (WHO). The strategy relies on repeated annual mass drug administration (MDA) of donated anti-filarial drugs (5-7 years of MDA with albendazole plus diethylcarbamazine or ivermectin) with the aim to reduce the reservoir of blood borne microfilaria (MF) below a level required for continuing transmission by local mosquito vectors. However, recent observations indicate that progress toward LF elimination is stalled and difficult to ascertain in many areas. This application will address two major deficiencies. The first is a lack of robust methods for monitoring and evaluation that allow for informed decision making with respect to a) whether MDA should be continued or stopped and b) how vector control measures (such as long lasting insecticide treated bednets; LLIN) will accelerate elimination using MDA. Existing national LF elimination programs are based on the WHO recommended Binax rapid card test, which detects adult Wb antigen in the blood. Although this card test is rapid and convenient, it often produces high false positive and false negative rates following MDA when compared to parasitological assays, more sensitive parasite-antigen specific serological assays. The second deficiency is lack of robust quantitative data assessing of the relative added benefit of combining vector control using LLIN with MDA to reduce LF transmission. In the current application we combine >25 years experience and access to a large archive of samples obtained in studying LF transmission in Papua New Guinea (PNG) using novel antigens provided by colleagues at NIH and the recent introduction of LLINs in PNG for malaria control in a endemic area where the vectors for malaria and LF are the same. This study a) characterizes the critical variables and monitoring tools for LF elimination, b) quantifies the impact of LLIN on LF elimination programs using MDA, and c) links entomological and human markers of LF transmission during LF elimination monitoring. Effective LF elimination monitoring tools and strategies as tested in this study are essential to achieving and maintaining LF elimination in PNG and the stated 2020 goals of the Global Program for the Elimination of LF (GPELF). PUBLIC HEALTH RELEVANCE: Progress toward LF elimination is difficult to ascertain due to poor understanding of the optimal monitoring tools needed to inform decision making with respect to a) whether MDA should be continued or stopped and b) how vector control measures (such as insecticide treated bednets; LLIN) will accelerate elimination using MDA. This RO1 application will test lymphatic filariasis monitoring tools and strategies in Papua New Guinea communities receiving mass drug administration with and without LLIN. Effective LF elimination monitoring tools and strategies as tested in this study are essential to achieving and maintaining LF elimination in PNG and the stated 2020 goals of the Global Program for the Elimination of LF (GPELF).